Anemia of Chronic Disease

KEY FEATURES

Essentials of Diagnosis

• Mild or moderate normocytic or microcytic anemia

• Normal or increased ferritin and normal or reduced transferrin

• Underlying chronic disease

General Considerations

• Many chronic systemic diseases are associated with mild or moderate anemia

• Anemia of inflammation

  • Associated with chronic inflammatory states, such as

    • Inflammatory bowel disease

    • Rheumatologic disorders

    • Chronic infections

    • Malignancy

  • Mediated through hepcidin (a negative regulator of ferroportin)

    • Primarily via elevated IL-6

    • Results in reduced iron uptake in the gut and

    • Reduced iron transfer from macrophages to erythroid progenitor cells in bone marrow

  • In addition there is

    • Reduced responsiveness to erythropoietin

    • Elaboration of hemolysins that shorten red blood cell survival

    • Production of inflammatory cytokines that dampen red cell production

• Anemia of organ failure

  • Can occur with

    • Chronic kidney disease

    • Hepatic failure

    • Endocrine gland failure

  • Erythropoietin production is reduced

    • Red blood cell mass decreases in response to

    • Diminished signal for red blood cell production

  • Serum iron is normal

    • Except in chronic kidney disease

    • Low due to reduced hepcidin clearance and

    • Subsequent enhanced degradation of ferroportin

• Anemia of older adults

  • Present in up to 20% of individuals over age 85 years

  • Thorough evaluation for an explanation of anemia is negative

  • A consequence of

    • Relative resistance to red blood cell production in response to erythropoietin

    • Decrease in erythropoietin production relative to the nephron mass

    • Dampening of erythropoiesis due to high levels of chronic inflammatory cytokines

    • Somatic pathogenic myeloid gene variations typically associated with myeloid neoplasms; this condition is referred to as clonal cytopenias of undetermined significance

  • Serum iron is normal

CLINICAL FINDINGS

Symptoms and Signs

• Clinical features are those of causative condition and anemia

• Suspect diagnosis in patients with known chronic diseases

DIAGNOSIS

Laboratory Tests

• Hematocrit rarely falls below 60% of baseline (except in end-stage kidney disease)

• Mean corpuscular volume (MCV) usually normal or slightly reduced

• RBC morphology

  • Usually normal

  • Reticulocyte count mildly decreased or normal

• In anemia of inflammation

  • Low serum iron

  • Low transferrin saturation

    • May be extremely low

    • Can lead to erroneous diagnosis of iron deficiency

  • Normal or increased serum ferritin

    • Serum ferritin < 30 mcg/L suggests coexistent iron deficiency

  • Diagnosing concomitant iron deficiency may be challenging

    • Serum ferritin can be as high as 200–500 ng/mL (450–1125 pmol/L)

    • Reticulocyte hemoglobin concentration < 28 pg

    • Bone marrow biopsy is diagnostic

  • In other anemias of chronic diseaseNormal or increased iron stores

  • Anemia of older persons is a diagnosis of exclusion

• Clonal cytopenias of undetermined significance

  • Diagnosed by sending blood or bone marrow sample for

  • Myeloid gene sequencing

• Note of caution: Certain circumstances of iron-restricted erythropoiesis (eg, malignancy) partially respond to parenteral iron infusion

  • Even when the iron stores are replete

  • Due to the rapid distribution of parenteral ...